Adenosine deaminase negative pleural tuberculosis: a case report.

BACKGROUND: A pleural fluid adenosine deaminase (ADA) has been used globally to assist in the diagnosis of a tuberculous pleural effusion (TPE) with a notable negative predictive value. CASE PRESENTATION: We report a case of a patient with a negative pleural fluid ADA who was found to have culture-positive and biopsy-proven Mycobacterium tuberculosis. CONCLUSIONS: This case shows the importance of pursuing gold standard diagnostic studies when clinical suspicion remains high despite negative preliminary testing. We further describe gaps in research to improve pleural fluid biomarkers for TPE.

Pleural fluid ADA activity in tuberculous pleurisy can be low in elderly, critically ill patients with multi-organ failure.

BACKGROUND: Adenosine deaminase (ADA) activity is typically elevated in patients with tuberculous pleural effusion (TPE), but low ADA has occasionally been reported in patients with TPE. The characteristics of these patients are not well-known, and erroneous exclusion of the possibility of TPE can result in a delayed diagnosis. This study investigated the characteristics of patients with TPE who had low ADA activity. METHODS: We retrospectively reviewed patients with microbiologically or pathologically confirmed TPE between 2012 to 2018 in a tertiary hospital in South Korea. Patients were categorised into two groups: high ADA (≥40 IU/L) and low ADA (< 40 IU/L). Clinical characteristics and Sequential Organ Failure Assessment (SOFA) scores were compared between groups. RESULTS: A total of 192 patients with TPE were included; 36 (18.8%) had ADA < 40 IU/L with a mean ADA activity level of 20.9 (±9.2) IU/L. Patients with low ADA were older (75.3 vs. 62.0 years, p < 0.001) and had a lower mean lymphocyte percentage (47.6% vs. 69.9%, p < 0.001) than patients with high ADA. Patients in the low ADA group had a significantly higher mean SOFA score (2.31 vs. 0.68, p < 0.001), and patients with organ dysfunction were significantly more common in the low ADA group (p < 0.001). Patients with 2 or ≥ 3 organ dysfunctions constituted 19.4 and 13.9% of the patients in the low ADA group, whereas they constituted 7.1 and 1.3% of the patients in the high ADA group (p < 0.001). Multivariate logistic regression analyses showed that older age (odds ratio = 1.030, 95% confidence interval 1.002-1.060, p = 0.038) and a higher SOFA score (odds ratio = 1.598, 95% confidence interval 1.239-2.060, p < 0.001) were significantly associated with low ADA activity in patients with TPE. CONCLUSIONS: ADA activity can be low in patients with TPE who are elderly, critically ill, and exhibit multiorgan failure. Low ADA activity cannot completely exclude the diagnosis of TPE, and physicians should exercise caution when interpreting pleural fluid exams.

Elevated Adenosine Dehydrogenase (ADH) and Positive Tuberculin Test Firstly Misdiagnosed as Tuberculous Pleural Effusion Finally Proved as Pleural Mesothelial Sarcoma by Thoracoscopic Biopsy Pathology: a Case Report and Literature Review.

BACKGROUND: In China, tuberculous pleural effusion is the most common cause for pleural effusion. Elevated ADH and positive tuberculin test usually are characteristic of tuberculous pleural effusion. We reported a 71-year-old male patient with elevated ADH and positive tuberculin test firstly misdiagnosed as tuberculous pleural effusion finally proven as pleural mesothelial sarcoma by thoracoscopic pathology. METHODS: Appropriate laboratory tests and thoracentesis were carried out. Thoracoscopy and pathological biopsy were performed to differentiate tuberculous pleural effusion. RESULTS: Chest CT showed right pleural effusion. ADH in pleural effusion was over 45 U/L and PPD test was positive. No abnormal cells were found in pleural effusion pathology. Pathology of thoracoscopic biopsy proved pleural mesothelioma. CONCLUSIONS: Elevated ADH and positive tuberculin test are not a specific index for tuberculosis and thoracoscopic biopsy pathology is crucial for differential diagnosis.

The diagnostic effect of sequential detection of ADA screening and T-SPOT assay in pleural effusion patients.

Purpose: To evaluate the diagnostic effect of sequential detection of Adenosine deaminase (ADA) screening and T-SPOT assay on tuberculosis (TB) pleurisy in pleural effusion patients. Materials and methods: 248 pleural effusion patients (172 TB and 76 non-TB) were retrospectively analyzed in the study. The concentrations of ADA and lactate dehydrogenase (LDH) were measured in pleural fluids and serum samples of the patients. T-SPOTT assays were performed in pleural fluids. The relationship between ADA, T-SPOT and the occurrence of TB pleurisy was evaluated using logistic regression analysis. Results: The level of pleural ADA and positive rate of T-SPOT were all higher in TB pleurisy group than non-TB pleurisy group (p < .001). The positive rate of T-SPOT detection reached 98.83% in the TB pleurisy group while only 40.7% in non-TB pleurisy group (p < .001). Additionally, 8 patients (4.65%) in the TB pleurisy group showed the level of pleurisy ADA exceeded 40 IU/L while only one patient (1.31%) in the non-TB pleurisy group. Conclusion: The sequential detection of ADA screening and T-SPOT assay was found to be an accurate and rapid method for identifying TB pleurisy from pleural effusion, which would promote effective treatment.

Tuberculosis pleural en paciente pediátrico: reporte de un caso y revisión de la literatura / Pleural tuberculosis in a pediatric patient: case report and review

Tuberculosis (TB) is a common cause of pleural effusion in young people from endemic areas. Among the forms of extrapulmonary TB in people with immunodeficiencies, the most frequent localization is the pleura. The use of immunological and molecular biology tests for the diagnosis of TB in pleural fluid and other locations with high sensitivity and specificity is highlighted. We present a clinical case with the objective of giving an overview of the treatment of the patient with suspected pleural tuberculosis

La Tuberculosis (TB) es una causa común de derrame pleural en jóvenes en zonas endémicas. Dentro de las formas de TB extrapulmonar en personas que cursan con inmunodeficiencias, la localización más frecuente es la TB pleural. Se destaca el uso de las pruebas inmunológicas y de biología molecular para el diagnóstico de TB en líquido pleural y de otras localizaciones con una elevada sensibilidad y especificidad. Se presenta un caso clínico con el objetivo de describir una visión general del abordaje del paciente con sospecha de tuberculosis pleural

Performance of clinical prediction rules for diagnosis of pleural tuberculosis in a high-incidence setting.

OBJECTIVES: Diagnosis of pleural tuberculosis (PT) is still a challenge, particularly in resource-constrained settings. Alternative diagnostic tools are needed. We aimed at evaluating the utility of Clinical Prediction Rules (CPRs) for diagnosis of pleural tuberculosis in Peru. METHODS: We identified CPRs for diagnosis of PT through a structured literature search. CPRs using high-complexity tests, as defined by the FDA, were excluded. We applied the identified CPRs to patients with pleural exudates attending two third-level hospitals in Lima, Peru, a setting with high incidence of tuberculosis. Besides pleural fluid analysis, patients underwent closed pleural biopsy for reaching a final diagnosis through combining microbiological and histopathological criteria. We evaluated the performance of the CPRs against this composite reference standard using classic indicators of diagnostic test validity. RESULTS: We found 15 eligible CPRs, of which 12 could be validated. Most included ADA, age, lymphocyte proportion and protein in pleural fluid as predictive findings. A total of 259 patients were included for their validation, of which 176 (67%) had PT and 50 (19%) malignant pleural effusion. The overall accuracy of the CPRs varied from 41% to 86%. Two had a positive likelihood ratio (LR) above 10, but none a negative LR below 0.1. ADA alone at a cut-off of ≥40 IU attained 87% diagnostic accuracy and had a positive LR of 6.6 and a negative LR of 0.2. CONCLUSION: Many CPRs for PT are available. In addition to ADA alone, none of them contributes significantly to diagnosis of PT.

Activation of calpain by renin-angiotensin system in pleural mesothelial cells mediates tuberculous pleural fibrosis.

Pleural fibrosis is defined as an excessive deposition of extracellular matrix (ECM) components that results in destruction of the normal pleural tissue architecture. It can result from diverse inflammatory conditions, especially tuberculous pleurisy. Pleural mesothelial cells (PMCs) play a pivotal role in pleural fibrosis. Calpain is a family of calcium-dependent endopeptidases, which plays an important role in ECM remodeling. However, the role of calpain in pleural fibrosis remains unknown. In the present study, we found that tuberculous pleural effusion (TPE) induced calpain activation in PMCs and that inhibition of calpain prevented TPE-induced collagen-I synthesis and cell proliferation of PMCs. Moreover, our data revealed that the levels of angiotensin (ANG)-converting enzyme (ACE) were significantly higher in pleural fluid of patients with TPE than those with malignant pleural effusion, and ACE-ANG II in TPE resulted in activation of calpain and subsequent triggering of the phosphatidylinositol 3-kinase (PI3K)/Akt/NF-κB signaling pathway in PMCs. Finally, calpain activation in PMCs and collagen depositions were confirmed in pleural biopsy specimens from patients with tuberculous pleurisy. Together, these studies demonstrated that calpain is activated by renin-angiotensin system in pleural fibrosis and mediates TPE-induced collagen-I synthesis and proliferation of PMCs via the PI3K/Akt/NF-κB signaling pathway. Calpain in PMCs might be a novel target for intervention in tuberculous pleural fibrosis.

A diagnostic algorithm for tuberculous pleurisy using the ELISPOT assay on peripheral blood and pleural effusion.

BACKGROUND: Diagnosis of tuberculous (TB) pleurisy remains challenging due to the paucibacillary nature of the disease. We prospectively assessed the diagnostic usefulness of the T-cell based ELISPOT assay, and created a clinical algorithm for differentiating TB pleurisy from other diagnoses. METHODS: All adult patients with suspicion for TB pleurisy were enrolled in a tertiary hospital in Seoul, South Korea, over a 7-year period. ELISPOT assays were performed using mononuclear cells from peripheral blood and pleural effusion. RESULTS: Seventy-seven patients with suspected TB pleurisy were enrolled. Of these, 33 (43%) patients, comprising 27 confirmed and 6 probable TB pleurisy, were classified as TB pleurisy, and 36 (47%) were classified as not TB. The remaining 8 with possible TB pleurisy were excluded from the final analysis. The sensitivities and specificities, respectively, of the diagnostic methods were as follows: pleural fluid adenosine deaminase (ADA) level 32 U/L, 81% and 79%; peripheral blood mononuclear cells (PBMC) ELISPOT assay, 82% and 73%; pleural effusion-mononuclear cells (PE-MC) ELISPOT assay, 58% and 87%. When the diagnostic algorithm was applied, PBMC ELISPOT ≥6 spots or ADA ≥32 U/L' as a rule-out test safely excluded 46% (12/26) of the not TB patients, and 'PE-MC ≥6 spots' as a rule-in test accurately classified 23% (7/31) of the patients with TB pleurisy. CONCLUSIONS: A diagnostic algorithm combining ELISPOT assays and ADA levels in pleural fluid appears to be a promising and non-invasive approach for patients with suspected TB pleurisy.

Can pleural adenosine deaminase (ADA) levels in pleural tuberculosis predict the presence of pulmonary tuberculosis? A CT analysis.

AIM: To assess the relationship between imaging features of pulmonary tuberculosis at computed tomography (CT) and adenosine deaminase (ADA) values via pleural fluid analysis in patients with pleural tuberculosis. MATERIALS AND METHODS: This retrospective study enrolled 60 patients who underwent fluid analysis for ADA and chest CT and were diagnosed with tuberculosis by culture or polymerase chain reaction of pleural fluid and sputum. The presence of centrilobular nodules, consolidation, cavitation, and mediastinal lymphadenopathy at CT were evaluated. The relationship between ADA values and the pattern of pulmonary involvement of tuberculosis was analysed. RESULTS: Pulmonary involvement was seen in 42 of the 60 patients. A centrilobular nodular pattern was seen in 37 and consolidation in 22. In 17 patients, both findings were identified. A centrilobular nodular pattern was more common than consolidation or cavitary lesions. When ADA values were high, pulmonary involvement was more frequent (p=0.002). Comparing low and high ADA groups using an obtained cut-off value of 80 IU/l, the high group had more frequent pulmonary involvement (p<0.001). CONCLUSION: Patients with tuberculous pleurisy who had high ADA values had a higher probability of manifesting pulmonary tuberculosis. High ADA values may help predict contagious pleuroparenchymal tuberculosis. The most common pulmonary involvement of tuberculous pleurisy showed a centrilobular nodular pattern.

Pleural effusion adenosine deaminase is not accurate in diagnosis of pediatric tuberculous pleural effusion: a retrospective study.

OBJECTIVE: Pleural effusion (PE) adenosine deaminase (ADA) has good performance in detection of tuberculous pleural effusion (TPE). However, few study was conducted for its value in pediatric patients. To evaluate PE ADA in diagnosis of pediatric TPE, a retrospective study was performed. PATIENTS AND METHODS: 204 pediatric PE patients were enrolled, and then were grouped into TPE group (77 cases, aged 11.51 ± 0.40 years) and non-TPE group (127 cases, aged 6.39 ± 0.35 years). Man-Whitney U test was used to compare difference in pleural ADA between the two groups. The correlation between age and ADA activity was analyzed by Spearman's correlation coefficient analysis. RESULTS: In our study, there was no difference in pleural ADA between TPE (62.1 ± 4.2 U/L) and non-TPE patients (87.7 ± 10.0 U/L). Compared with empyema patients (183.8 ± 30.0 U/L), pleural ADA was lower in parapneumonic effusion (PPE) patients (63.4 ± 3.8, p < 0.01), or TPE patients (p <0.01). Correlation analysis showed that there were no correlation between age and pleural ADA within TPE, PPE or both patients (all p > 0.05). Meanwhile, there was no significant difference in PE ADA level between genders. CONCLUSIONS: Considering the fact that the majority of pediatric PEs is TPE and PPE, our study suggests that PE ADA isn't accurate in detection of pediatric TPE. Meanwhile, an extremely high ADA activity should raise suspicion of empyema or lymphoma.

Tissue inhibitor of metalloproteinase-1 is responsible for residual pleural thickening in pleural tuberculosis.

Residual pleural thickening (RPT) is the most frequent complication associated with pleural tuberculosis, and may occur even after successful anti-tuberculosis medications. Matrix metalloproteinases (MMPs) are zinc-dependent proteinases capable of degrading all components of the extracellular matrix. The proteolytic action of MMPs may be involved in the pathogenesis of tuberculosis. MMP-9, secreted by monocytes and lymphocyte, may lead to long-term fibrosis. The aim of the present study was to determine whether MMP-2 and/or MMP-9 and their specific inhibitors, tissue inhibitors of metalloproteinase 1 (TIMP-1) and TIMP-2, could be used to predict RPT. This retrospective study enrolled 52 patients diagnosed with pleural tuberculosis. Levels of MMP-2, MMP-9, TIMP-1, and TIM-2 were determined in the pleural fluid by ELISA. The RPT was measured on chest X-ray at the completion of treatment and the final follow-up. The average periods of anti-tuberculosis medication and the follow-up after completion of treatment were 6.7 and 7.6 months, respectively. MMP-2 or MMP-9 levels had no significant correlation to RPT. The patients with RPT > 2 mm at the completion of anti-tuberculosis medication and the final follow-up had higher TIMP-1 levels (p = 0.00 and p = 0.001, respectively). However, patients with RPT > 2 mm at the completion of anti-tuberculosis medication had lower TIMP-2 levels (p = 0.005). In a logistic regression model, elevated TIMP-1 levels at the completion of anti-tuberculosis medications were associated with RPT. In conclusion, higher TIMP-1 levels are responsible for the development of RPT and may be helpful for predicting RPT in pleural tuberculosis.

Role of adenosine deaminase and the influence of age on the diagnosis of pleural tuberculosis.

OBJECTIVE: 1) To determine factors affecting adenosine deaminase (ADA) levels in pleural fluid (PF), and 2) to establish the optimal ADA cut-off level for a Brazilian population. DESIGN: ADA levels in PF of 309 patients were analysed to investigate pleural effusion. All patients were evaluated for age, sex and presence of tuberculosis (TB) based on a positive pleural biopsy. Differences in ADA levels between groups were analysed using Kruskal-Wallis one-way analysis of variance. Logistic regression analysis was also carried out to predict the occurrence of TB. ADA cut-off levels were selected using the receiver operating characteristic (ROC) curve. RESULTS: The mean PF ADA level was significantly higher in the tuberculous pleural group than in non-tuberculous pleural patients (63.3 ± 29 IU/l vs. 19 ± 31 IU/l, P < 0.001). There was a significant correlation between PF ADA levels and age: for patients aged ⩾45 years, the ROC curve for ADA had an area under the curve of 0.91. An ADA level of 29 IU/l resulted in a sensitivity of 88.6% and specificity of 91.5%. CONCLUSIONS: There is a significant negative correlation between PF ADA level and age. The use of a lower ADA cut-off reduces the number of false-negative results.

Factors influencing pleural adenosine deaminase level in patients with tuberculous pleurisy.

BACKGROUND: Adenosine deaminase (ADA) activity is useful for diagnosing tuberculous (TB) pleurisy in regions with a high prevalence of tuberculosis. However, some cases of TB pleural effusion show decreased ADA activity. Therefore, we evaluated factors influencing pleural ADA levels in patients with TB pleurisy. METHODS: We retrospectively evaluated 182 patients with TB pleural effusion who were admitted to Gyeongsang National University Hospital from January 2004 to September 2008. Patients were dichotomized into 2 groups: a low-ADA (<40 IU/L) group (n = 22) and a high-ADA (≥40 IU/L) group (n = 160). Age, sex, ADA level of pleural effusion, smoking status, history of tuberculosis and comorbid diseases were evaluated in each group. RESULTS: The median age of the patients was 50.5 years, with a male to female ratio of 1.72:1. Patients with a low-ADA level were significantly older than those with a high ADA level (66.9 ± 12.0 versus 49.4 ± 21.2 years, P < 0.001). A history of tuberculosis and hypertension was more common in the low-ADA group than in the high-ADA group (31.8% versus 15.0%, P = 0.049 and 36.4% versus 16.9%, P = 0.03, respectively). A multivariate analysis revealed that older age and current smoking were predictive of TB pleurisy with a low ADA level (odds ratios, 1.053 and 4.848; P = 0.002 and 0.028, respectively). CONCLUSIONS: Physicians should be careful when interpreting pleural ADA levels in elderly patients and/or current smokers for the diagnosis of TB pleurisy.

Influence of storage time on pleural fluid adenosine deaminase activity.

BACKGROUND: Storing pleural fluid samples for research purposes is a common practice, but whether adenosine deaminase (ADA), an enzyme used for the diagnosis of tuberculous pleuritis, is stable over long periods of time is unknown. METHODS: We evaluated the stability of pleural ADA concentrations in 223 samples frozen at -800C as compared to values obtained immediately following the initial thoracentesis. Sample storage time ranged from several months to slightly more than 10 years. RESULTS: ADA activity was stable for up to 2.6 years. Afterwards, it decreased 6 to 8 U/L, enough to drop 2 (3.3%) tuberculous patients below the diagnostic ADA cutoff. CONCLUSIONS: As far as ADA enzymatic activity is concerned, pleural fluid samples are viable for extended periods of time. However, some caution in interpreting results from specimens stored for > 2.6 years is prudent.

Role of adenosine deaminase in diagnosis of tubercular pleural effusion.

The diagnosis of pleural tuberculosis (TB) continues to be a challenge in clinical practice. Traditional diagnostic methods are very useful for the diagnosis of pulmonary TB but have a low yield when applied to pleural fluid. It is produced during the inflammatory process triggered by the M. tuberculosis. Usefulness of adenosine deaminase (ADA) estimation in pleural fluid has been shown as a reliable chemical bio-marker specially when there is suspicion of tuberculosis in endemic areas. ADA level was determined in the pleural fluid of 100 patients present with pleural effusion admitted at Mymensingh Medical College Hospital during the period of March 2012 to September 2012. ADA level was >40IU/L among the 52 tubercular pleural effusion patients with sensitivity & specificity is 100% and 66% respectively. Thus is evident that ADA level can be used along with conventional methods for diagnosis of pleural TB.

Factors affecting pleural fluid adenosine deaminase level and the implication on the diagnosis of tuberculous pleural effusion: a retrospective cohort study.

BACKGROUND: Adenosine deaminase (ADA) is useful in the diagnosis of tuberculous pleural effusion (TPE). This study aims to determine the factors affecting pleural fluid ADA levels and to establish the optimal ADA levels for diagnosis of TPE for different age groups. METHODS: This was a retrospective study from January 2007 to October 2011. One hundred and sixty patients who had pleural fluid ADA performed for investigation of pleural effusion were analyzed. Variables examined included demographics, pleural fluid characteristics and peripheral blood counts. The ADA cut-offs according to age were selected using the receiver operating characteristic (ROC) curve. RESULTS: The mean pleural fluid ADA was significantly higher in the TPE group (100 ± 35 IU/L) compared to non TPE patients (30 ± 37 IU/L). There was significant correlation between pleural fluid ADA and age, pleural fluid protein, LDH, and fluid absolute lymphocyte count. The strongest correlation was seen with age (r = -0.621). For patients ≤ 55 years old the ROC for ADA had area under curve (AUC) of 0.887. A pleural fluid ADA of 72 IU/L had sensitivity of 95.1%, specificity of 87.5%, positive predictive value (PPV) of 95.1% and negative predictive value (NPV) of 87.5% for the diagnosis of TPE. For patients > 55 years old the AUC is 0.959. ADA of 26 IU/L had a sensitivity of 94.7%, specificity of 80.4%, PPV of 62% and NPV of 97.8%. CONCLUSIONS: There is a significant negative correlation between pleural fluid ADA and age. For older patients, a lower ADA cut-off should be used to exclude TPE.

Indoleamine 2,3-dioxygenase in the pathogenesis of tuberculous pleurisy.

BACKGROUND: Pleural fluid is a frequent manifestation in pulmonary diseases, such as lung cancer and infectious diseases, including pulmonary tuberculosis (TB). The enzyme indoleamine 2,3-dioxygenase (IDO) catalyses tryptophan through the kynurenine pathway, and is considered a crucial immunoregulatory molecule mediating immune tolerance. Recent studies have shown IDO activity to be a novel prognostic factor not only in cancer patients but also in those with infectious diseases, including pneumonia and pulmonary TB. However, no studies have measured and determined the clinical significance of IDO activity in pleural fluid. METHODS: We enrolled 92 patients, including 34 with tuberculous pleurisy (TBP), 36 with malignant pleuritis and 15 with parapneumonic effusions. IDO activity was evaluated using liquid chromatography/electrospray ionisation tandem mass spectrometry, and was estimated by calculating kynurenine-to-tryptophan ratio. RESULTS: Pleural fluid from patients with TBP had significantly higher kynurenine concentrations and significantly lower tryptophan concentrations, resulting in significantly higher IDO activity compared with pleural effusion or serum from non-tuberculous pleuritis (all P < 0.001). Pleural tissue from TBP showed enhanced IDO expression in epithelioid granuloma regions by immunohistochemistry. CONCLUSIONS: These results suggest that IDO is strongly involved in the pathogenesis of TBP.

Clinical impact and reliability of carbonic anhydrase XII in the differentiation of malignant and tuberculous pleural effusions.

OBJECTIVE: To assess the practical utility of pleural fluid carbonic anhydrase XII (CAXII) quantification for differential diagnosis of effusions. MATERIALS AND METHODS: Fluid was collected prospectively from fifty patients presenting with lymphocytic pleural effusions for investigation and CAXII was quantified by ELISA. RESULTS: Pleural fluid CAXII concentrations were significantly higher in lung cancer patients (n=30) than in tuberculous controls (n=20). The sensitivity and specificity of this biomarker were 60%and 75%, respectively. CAXII measurement was not inferior to cytological examination in the diagnosis and exclusion of pleural effusions from lung cancer patients (sensitivity 60% vs. 57%; specificity 75% vs. 100%; positive predictive value 77%; negative predictive value 54%). In patients with negative cytology, it offered a sensitivity of 54%. CONCLUSIONS: Pleural fluid CAXII is elevated in pleural effusions from lung cancer patients. Measurement of CAXII may be used in the future as a valuable adjunct to cytology in the diagnostic assessment of patients with pleural effusions related to lung cancer, especially when cytological examination is inconclusive.

When pleural potassium exceeds 5.0 mEq/L, high pleural adenosine deaminase levels do not necessarily indicate tuberculous pleuritis.

BACKGROUND AND OBJECTIVE: The aim of this study was to determine whether high levels of pleural adenosine deaminase (pADA) are predictive for tuberculosis when pleural effusions do not satisfy the criteria for lymphocytic effusions or show neutrophil predominance. METHODS: This was a retrospective observational study of 147 consecutive patients with exudative pleural effusions that were diagnosed by analysis of fluid samples during a 3-year period from 1 April 2007 to 31 March 2010. Multiple linear correlation tests were used to assess clinical variables as possible predictors of high pADA levels. RESULTS: High pleural LDH (pLDH) and pleural potassium (pK) levels were associated with high pADA levels (P < 0.0001). Although there was a linear correlation between pLDH and pADA levels in patients with parapneumonic effusions (PPE) (n = 75), tubercular effusions (n = 21), malignant effusions (n = 41) and miscellaneous effusions (n = 10), a significant linear correlation between pK and pADA levels was observed only in patients with PPE (ρ = 0.525, P < 0.0001). When the cut-off value for pK was set at 5.0 mEq/L, pADA levels were >50 IU/L and pK levels were >5.0 mEq/L in only one patient (5%) in the tuberculosis group (n = 21) and 15 patients (12%, all with PPE) in the non-tuberculosis group (n = 126). CONCLUSIONS: When pK levels exceed 5.0 mEq/L, high pADA levels do not necessarily indicate the presence of tuberculous pleuritis.

Predictive role of adenosine deaminase for differential diagnosis of tuberculosis and malignant pleural effusion in Turkey.

Tuberculous pleural effusion (TPE) is a common problem for differential diagnosis from malignant effusion (MPE) in epidemic areas of tuberculosis (TB). Prediction based on adenosine deaminase (ADA) is dependent on age as well as the tuberculosis incidence. The aim of the study was to evaluate cutoff values for ADA with sensitivity and specificity results for the differential diagnosis of MPE and TPE in a population with intermediate incidence of TB. We retrospectively analysed 196 patients with a definitive diagnosis of TPE (n = 114) and MPE (n = 82). The optimal cutoff value of ADA was determined using the receiver operating characteristic (ROC) curve. There was a statistically significant difference according to the levels of pleural fluid ADA between TPE and MPE groups (p < 0.0001). The cutoff value for diagnosing TPE was > 55 U/L, with a sensitivity = 86.8%, specificity = 86.6%, positive predictive value (PPV) = 90%, negative predictive value (NPV) = 82.6% and accuracy = 82.6%. We then combined ADA > 55 U/L and age < 50 and were able to discriminate the TPE group with increased specifity (95.7 %) and PPV (98.8%) results. The model could correctly classify 21 MPE out of 23 and 82 TPE out of 94 patients. A pleural fluid ADA value < 31 U/L suggests that TPE is highly unlikely with a sensitivity = 43.9 %, specificity = 100%, PPV = 100%, NPV = 71.3% and accuracy = 76.6%. It can be concluded that ADA is a very useful parameter for the differential diagnosis of TPE and MPE, specifically in youngers with a higher incidence of tuberculosis.